Burden of female breast cancer in India: estimates of YLDs, YLLs, and DALYs at national and subnational levels based on the national cancer registry programme.

PURPOSE: Female breast cancer (BC) is the leading cause of cancer incidence and mortality in India, and accounted for 13.5% of new cancer cases and 10% of cancer-related deaths in 2020. This study aims to estimate and report the female BC burden in India at state level from 2012 to 2016 in terms of years of life lost, years lived with disability, and disability-adjusted life years (DALYs), and to project the burden for the year 2025. METHODS: The cancer incidence and mortality data from 28 population-based cancer registries were analysed. The mean mortality to incidence ratio was estimated, and mortality figures were adjusted for underreporting. The burden of female BC was estimated at national and subnational levels using Census data, World Health Organisation's lifetables, disability weights, and the DisMod-II tool. A negative binomial regression is employed to project burden for 2025. RESULTS: The burden of BC among Indian women in 2016 was estimated to be 515.4 DALYs per 100,000 women after age standardization. The burden metrics at state level exhibited substantial heterogeneity. Notably, Tamil Nadu, Telangana, Karnataka, and Delhi had a higher burden of BC than states in the eastern and north-eastern regions. The projection for 2025 indicates to a substantial increase, reaching 5.6 million DALYs. CONCLUSION: The female BC burden in India was significantly high in 2016 and is expected to substantially increase. Undertaking a multidisciplinary, context-specific approach for its prevention and control can address this rising burden.

A Multicenter Retrospective Cohort Study to Characterize Patients Hospitalized With Multisystem Inflammatory Syndrome in Adults and Coronavirus Disease 2019 in the United States, 2020-2021.

BACKGROUND: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management. METHODS: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10 223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.

Burden of cancers in India - estimates of cancer crude incidence, YLLs, YLDs and DALYs for 2021 and 2025 based on National Cancer Registry Program.

BACKGROUND: Cancer is the major cause of morbidity and mortality worldwide. The cancer burden varies within the regions of India posing great challenges in its prevention and control. The national burden assessment remains as a task which relies on statistical models in many developing countries, including India, due to cancer not being a notifiable disease. This study quantifies the cancer burden in India for 2016, adjusted mortality to incidence (AMI) ratio and projections for 2021 and 2025 from the National Cancer Registry Program (NCRP) and other publicly available data sources. METHODS: Primary data on cancer incidence and mortality between 2012 and 2016 from 28 Population Based Cancer Registries (PBCRs), all-cause mortality from Sample Registration Systems (SRS) 2012-16, lifetables and disability weight from World Health Organization (WHO), the population from Census of India and cancer prevalence using the WHO-DisMod-II tool were used for this study. The AMI ratio was estimated using the Markov Chain Monte Carlo method from longitudinal NCRP-PBCR data (2001-16). The burden was quantified at national and sub-national levels as crude incidence, mortality, Years of Life Lost (YLLs), Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). The projections for the years 2021 and 2025 were done by the negative binomial regression model using STATA. RESULTS: The projected cancer burden in India for 2021 was 26.7 million DALYsAMI and expected to increase to 29.8 million in 2025. The highest burden was in the north (2408 DALYsAMI per 100,000) and northeastern (2177 DALYsAMI per 100,000) regions of the country and higher among males. More than 40% of the total cancer burden was contributed by the seven leading cancer sites - lung (10.6%), breast (10.5%), oesophagus (5.8%), mouth (5.7%), stomach (5.2%), liver (4.6%), and cervix uteri (4.3%). CONCLUSIONS: This study demonstrates the use of reliable data sources and DisMod-II tools that adhere to the international standard for assessment of national and sub-national cancer burden. A wide heterogeneity in leading cancer sites was observed within India by age and sex. The results also highlight the need to focus on non-leading sites of cancer by age and sex. These findings can guide policymakers to plan focused approaches towards monitoring efforts on cancer prevention and control. The study simplifies the methodology used for arriving at the burden estimates and thus, encourages researchers across the world to take up similar assessments with the available data.

Crosslinked flagella as a stabilized vaccine adjuvant scaffold.

BACKGROUND: Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine scaffold as it is known to provide adjuvant activity through its TLR5 and inflammasome activation. Moreover, polymerized flagellin filaments can elicit a more robust immunoglobulin response than monomeric flagellin, and the multimeric antigen form can also promote T cell-independent antibody responses. Here, we aim to produce and test a covalently stabilized polymerized flagellar filament, providing additional immune efficacy through stabilization of its polymeric filament structure, as well as stabilization for long-term storage. RESULTS: Computational modeling of monomer packing in flagellin filaments helped identify amino acids with proximity to neighboring flagella protofilaments. Paired cysteine substitutions were made at amino acids predicted to form inter-monomer disulfide cross-links, and these substitutions were capable of forming flagella when transfected into a flagellin-negative strain of Salmonella enterica subspecies Typhimurium. Interestingly, each paired substitution stabilized different helical conformational polymorphisms; the stabilized filaments lost the ability to transition between conformations, reducing bacterial motility. More importantly, the paired substitutions enabled extensive disulfide cross links and intra-filament multimer formation, and in one of the three variants, permitted filament stability in high acidic and temperature conditions where wild-type filaments would normally rapidly depolymerize. In addition, with regard to potential adjuvant activity, all crosslinked flagella filaments were able to induce wild-type levels of epithelial NF-κB in a cell reporter system. Finally, bacterial virulence was unimpaired in epithelial adherence and invasion, and the cysteine substitutions also appeared to increase bacterial resistance to oxidizing and reducing conditions. CONCLUSIONS: We identified amino acid pairs, with cysteine substitutions, were able to form intermolecular disulfide bonds that stabilized the resulting flagellar filaments in detergent, hydrochloric acid, and high temperatures while retaining its immunostimulatory function. Flagellar filaments with disulfide-stabilized protofilaments introduce new possibilities for the application of flagella as a vaccine adjuvant. Specifically, increased stability and heat tolerance permits long-term storage in a range of temperature environments, as well as delivery under a range of clinical conditions.

Clinical Outcomes in Revision Anterior Cruciate Ligament Reconstruction: A Meta-analysis.

PURPOSE: The purpose of this meta-analysis was to determine overall objective graft failure rate, failure rate by graft type (allograft vs autograft reconstruction), instrumented laxity, and patient outcome scores following revision anterior cruciate ligament (ACL) reconstruction. Outcomes of interest were collected for all studies meeting the study inclusion criteria, but lower-level studies (level III/IV) were not pooled for quantitative synthesis due to high levels of heterogeneity in these study populations. METHODS: A comprehensive search strategy was performed to identify studies reporting outcomes of revision ACL reconstruction. The primary outcome reported was graft failure. A meta-analysis comparing rate of failure by graft type was conducted using a random effects model. Studies also reported patient clinical outcome scores, including International Knee Documentation Committee (IKDC), Lysholm, and knee injury and osteoarthritis outcome scores (KOOS) and graft laxity. RESULTS: Eight studies with 3,021 patients (56% male, 44% female) with an average age of 30 ± 4 years and mean follow-up time of 57 months were included. The overall objective failure rate was 6% (95% confidence interval [CI], 1.8%-12.3%). Mean instrumented laxity as side-to-side difference was 2.5 mm (95% CI, 1.9-3.1 mm). Mean IKDC subjective score was 76.99 (95% CI, 76.64-77.34), mean KOOS symptoms score was 76.73 (95% CI, 75.85-77.61), and mean Lysholm score was 86.18 (95% CI, 79.08-93.28). The proportion of patients with IKDC grade A or B was 85% (95% CI, 77%-91%). When the available data for failure rate were analyzed by graft type, autograft reconstruction had a failure rate of 4.1% (95% CI, 2.0%-6.9%), similar to allograft reconstruction at 3.6% (95% CI, 1.4%-6.7%). CONCLUSIONS: In this meta-analysis, revision ACL reconstruction had failure rates similar to autograft or allograft reconstruction. Overall outcome scores for revision reconstruction have improved but appear modest when compared with primary ACL reconstruction surgery. LEVEL OF EVIDENCE: Meta-analysis of Level II studies, Level II.

Combined Tibial Tubercle Osteotomy and Medial Patellofemoral Ligament Reconstruction for Recurrent Lateral Patellar Instability in Patients With Multiple Anatomic Risk Factors.

PURPOSE: To report the outcomes for combined tibial tubercle osteotomy (TTO) and medial patellofemoral ligament (MPFL) reconstruction and assess for potential risk factors for recurrent instability and/or poor outcomes. METHODS: The medical record at our institution was reviewed for patients treated with MPFL reconstruction and TTO for recurrent lateral patellar instability from 1998 to 2014. Preoperative imaging was assessed for trochlear dysplasia according to the Dejour classification (high grade = B, C, D) and the presence of patella alta using the Caton-Deschamps ratio (>1.2). The indication for combined MPFL reconstruction and TTO was MPFL insufficiency and a lateralized tibial tubercle. Outcomes were determined by recurrent instability, return to sport, and Kujala and International Knee Documentation Committee (IKDC) scores. RESULTS: Thirty knees in 28 patients (14 M, 14 F) with a mean age of 22.6 ± 9.1 years (range, 13-51 years) were included with a mean follow-up of 48 ± 28 months (24-123 months). Seventy-three percent (22/30) had high-grade trochlear dysplasia, and 63% (19/30) had patella alta. One patient had a postoperative dislocation and 1 had a subluxation event. The Caton-Deschamps ratio decreased by a mean of 0.2 (P = .001), leaving 30% with postoperative patella alta. The mean postoperative scores were as follows: Tegner = 5 ± 2, Kujala = 89 ± 16 (45-100), and IKDC = 85 ± 17 (44-100). Eighty-three percent (15/18) returned to their preoperative sport. Female gender was a risk factor for lower IKDC (77.3 vs. 92.6, P = .01) and Kujala (82.2 vs. 95.0, P = .03) scores. Medialization greater than 10 mm was directly correlated to lower IKDC (P = .02) and Kujala (P = .01) scores. CONCLUSIONS: The combination of MPFL reconstruction and TTO in patients with trochlear dysplasia results in low recurrence of instability. Patients on average had good subjective outcomes and were able to return to sport. Female gender and tibial tubercle medialization greater than 10 mm were associated with worse outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Partial meniscectomy provides no benefit for symptomatic degenerative medial meniscus posterior root tears.

PURPOSE: Medial meniscus posterior root tears (MMPRTs) are recognized as a source of pain and dysfunction, but treatment options remain a challenge. The purpose of the study was to determine (1) the efficacy of partial meniscectomy to treat MMPRTs compared to a matched group of non-operatively treated MMPRTs, and (2) risk factors for worse clinical and radiographic outcome. METHODS: This retrospective comparative study was performed to include patients with complete, isolated MMPRTs with documented clinical symptoms and were treated with arthroscopic partial meniscectomy (PMM) and a minimum 2-year follow-up. These patients were then matched by age, gender, and BMI to patients with the same diagnosis who were treated non-operatively. Clinical and radiographic outcomes were compared between the two groups. Analysis was performed to determine risk factors for worse clinical and radiographic outcome in the PMM group alone. RESULTS: Overall, 52 patients were included in the study. Twenty-six patients (9M:17F) with a mean age of 55 ± 9 and a mean BMI of 32.8 ± 5.3 were treated with PMM and followed for 5.5 ± 2.0 years (range 2.3-9.3 years). In the PMM group, final median Tegner score was 3, mean IKDC score was 67.8 ± 20, and more patients had grade II or higher arthritis at final follow-up than baseline (91.3 vs. 36%, p < 0.01). Overall, 14 of the 26 patients (54%) treated operatively progressed to total knee arthroplasty at a mean of 54.3 months. There was no significant difference in final Tegner scores, IKDC, K-L grades, progression to arthroplasty, or overall failure rate between the PMM group and non-operative group. Following PMM, female patients had lower final IKDC scores (44.0 ± 2.8 vs. 74.6 ± 16.7, p = 0.02) compared to males, as well as a higher rate of arthroplasty (70.6 vs. 20.0%, p = 0.009). Higher BMI correlated with lower IKDC scores (r = -0.91, p = 0.01) and meniscal extrusion was associated with higher rate of arthritis at final follow-up (p = 0.02). CONCLUSION: Partial meniscectomy for a complete MMPRT provides no benefit in halting arthritic progression. Patients who undergo PMM for MMPRTs still progress to significant arthritis, poor clinical outcomes and a high arthroplasty rate (54%) at over 5-year follow-up. Female gender, increased BMI, and meniscus extrusion were associated with worse outcome. STUDY DESIGN: Level III.

Poly-traumatic multi-ligament knee injuries: is the knee the limiting factor?

PURPOSE: Multi-ligament knee injuries (MLKI) from a high-velocity accident are rare but potentially devastating. This matched cohort analysis compares knee functional outcomes after multiple ligament reconstruction in poly-trauma patients to those that occurred in isolation. METHODS: Sixty-two patients with MLKI that occurred either as a component of polytrauma or had occurred in isolation were matched according to age, sex, and knee dislocation grade. Functional outcomes and knee physical examination were assessed at a 2-year follow-up. New Injury Severity Score (NISS) was calculated based on the poly-traumatic injury pattern. Risk factors for worse outcomes in the poly-trauma cohort were analyzed. RESULTS: The mean IKDC, Lysholm, and NISS scores in the polytrauma cohort were 57.2 ± 21.9, 62 ± 22, and 40.9 ± 20.4, respectively, at a mean of 67 months (range 24-220). The isolated knee injury group was followed for a mean of 74 months (range 24-266) with mean IKDC and Lysholm scores of 71.1 ± 26.5 and 78 ± 23, respectively. Patients in the control cohort had significantly higher IKDC (p = 0.01) and Lysholm scores, (p = 0.003). There were no major differences between the two groups in regards physical examination findings at final follow-up. None of the analyzed risk factors was predictive of poor outcome. CONCLUSION: When comparing knees with similar multi-ligament and neurovascular injury patterns, patients who sustained their injury as a result of poly-trauma demonstrated significantly lower functional scores following reconstruction. This is despite restoration of similar knee stability and range of motion. The functional outcomes following MLKI reconstruction in poly-traumatized patients are influenced by factors other than the knee including concomitant injuries and psychosocial factors. LEVEL OF EVIDENCE: Therapeutic Level III.

Functional testing and return to sport following stabilization surgery for recurrent lateral patellar instability in competitive athletes.

PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction and tibial tubercle osteotomy are commonly used to treat recurrent lateral patellar instability, yet there are limited available data on return to sport (RTS) following these procedures. The purpose of this study is to evaluate patient factors associated with excellent functional outcomes, including successful RTS, following surgical stabilization including MPFL reconstruction in competitive athletes with recurrent lateral patellar instability. METHODS: Athletes undergoing primary MPFL reconstruction for recurrent lateral instability from 2005 to 2013 were identified at a single institution. Concomitant procedures, such as tibial tubercle osteotomy (TTO), were included. Patient demographic information, including BMI, gender, age, and pre-injury Tegner score, was recorded. In addition, radiographs were reviewed for pre-operative patellar height (Caton-Deschamps index) and trochlear dysplasia (Dejour classification). All patients underwent a standardized rehabilitation/post-operative protocol, with isokinetic strength and functional testing being performed at 6 months post-operatively. Final Tegner scores, RTS status, subjective instability ratings, and Kujala scores were collected at a minimum of 2 years. Chi-squared analysis for categorical variables and Wilcoxon rank-sum analysis for continuous variables were used to determine the relationship between the previously mentioned patient and knee characteristics with isokinetic data, RTS status, or Kujala scores. RESULTS: Thirty-nine athletes (23 male, 16 female) at a mean age of 17.5 ± 2.9 years (range, 13-26) underwent primary MPFL reconstruction (32 autografts, seven allografts) for recurrent patellar instability with a mean follow-up of 47.0 ± 16.4 months. Sixteen patients (41%) underwent concomitant tibial tubercle osteotomies. Isokinetic data collected at 6 months post-operatively demonstrated mean knee flexion and extension strength deficits of 15.8 ± 10.1% and 21.4 ± 14.3%, respectively, compared to the contralateral leg (p < 0.001 for both). Patients who underwent concomitant tibial tubercle osteotomy (p = 0.04), males (p = 0.01) and those with patella alta (p = 0.04) had weaker 6-month isokinetic testing. Thirty-three of the thirty-nine (85%) athletes were able to RTS at a mean of 8.1 ± 3.9 months. Patients undergoing MPFL with concomitant TTO (p = 0.02) returned to sport at a slower rate. One patient (3%) reported an episode of recurrent dislocation requiring revision surgery. Kujala and Tegner scores at final follow-up were 91.1 ± 6.3 and 6 (range, 4-9), respectively. CONCLUSION: Surgical stabilization including MFPL reconstruction for recurrent lateral patellar instability is an effective procedure for returning athletes to competitive sports. However, strength deficits persist at 6 months after surgery, especially in those undergoing concomitant TTO, which may delay return to sport. Physicians can use these results to counsel patients that return to competitive sports is safe with good clinical outcomes and low rate of recurrence at 4-year follow-up; however, predisposing factors, like a lateralized tibial tubercle, should be addressed if necessary, but athletes should be counselled that a slower recovery and longer return to sport time may be expected. LEVEL OF EVIDENCE: IV.

AESOP: A Python Library for Investigating Electrostatics in Protein Interactions.

Electric fields often play a role in guiding the association of protein complexes. Such interactions can be further engineered to accelerate complex association, resulting in protein systems with increased productivity. This is especially true for enzymes where reaction rates are typically diffusion limited. To facilitate quantitative comparisons of electrostatics in protein families and to describe electrostatic contributions of individual amino acids, we previously developed a computational framework called AESOP. We now implement this computational tool in Python with increased usability and the capability of performing calculations in parallel. AESOP utilizes PDB2PQR and Adaptive Poisson-Boltzmann Solver to generate grid-based electrostatic potential files for protein structures provided by the end user. There are methods within AESOP for quantitatively comparing sets of grid-based electrostatic potentials in terms of similarity or generating ensembles of electrostatic potential files for a library of mutants to quantify the effects of perturbations in protein structure and protein-protein association.

Editorial Commentary: The Anterolateral Ligament-What We Know, What We Do Not Know, and How This Article Helps.

A recent study on knee anterolateral ligament anatomy is a significant contribution to the literature because it provides precise isometric radiographic landmarks for both femoral and tibial tunnel placement, which are paramount to successful anterolateral ligament reconstruction.

Return to Sport and Clinical Outcomes After Hip Arthroscopic Labral Repair in Young Amateur Athletes: Minimum 2-Year Follow-Up.

PURPOSE: To determine the rate of return of young amateur athletes to sport after hip arthroscopy, their clinical outcomes, and pathologic risk factors for worse outcomes 2 years after surgery. METHODS: This study included all patients between age 13 and 23 who participated in a sport prior to surgery with intent to return who underwent hip arthroscopy after failure of comprehensive nonoperative management for whom 2-year outcome scores were available. Outcomes collected retrospectively included modified Harris Hip Score (mHHS) and the Hip Outcome Scores (HOS) subscales for activities of daily living (ADL) and sport (HOS Sport). In addition, sport played, return to sport rates, and Tegner Scores were measured preinjury and postoperatively. Descriptive statistics were used to present demographic data. A priori analysis was used to determine the sample size needed to show minimal clinically important differences for mHHS, HOS ADL, and HOS Sport. RESULTS: The study population included 50 patients with a mean age of 17.8 years. Athletes returned to sport at a rate of 92% (46/50). At a mean follow-up of 34 months, the mean mHHS, HOS ADL, and HOS Sport outcome scores were 85, 91, and 80 for the entire study group; 87, 92, and 84 for the group that returned to sport; and 67, 82, and 41 for the group that did not return to sport, respectively. Median preinjury and postoperative Tegner levels were 8 and 7, respectively. Labral takedown and reattachment was associated with lower HOS ADL (P = .01) and HOS Sport scores (P = .02). CONCLUSIONS: Athletes returned to sport at a high rate (92%; 46/50) after hip arthroscopy and perform activities at near preinjury levels. In this group of athletes, arthroscopic labral repair with chondrolabral preservation, which reflected less severe chondrolabral pathology, performed better than labral repair with takedown and reattachment. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Non-operative management of medial meniscus posterior horn root tears is associated with worsening arthritis and poor clinical outcome at 5-year follow-up.

PURPOSE: Medial meniscus posterior root tears (MMPRTs) are a significant source of pain and dysfunction, but little is known about the natural history and outcome and for non-operative management of these lesions. The purpose of this study was to evaluate (1) the mid-term clinical and radiographic outcomes of non-operative treatment of MMPRTs and (2) risk factors for worse outcomes. METHODS: A retrospective review was performed for patients with symptomatic, unrepaired MMPRTs and a minimum 2-year follow-up for IKDC and Tegner outcome scores. Baseline and final radiographs were reviewed and graded according to Kellgren-Lawrence scores. Baseline MRIs were reviewed for the presence of meniscal extrusion, subchondral oedema, and insufficiency fractures. Failure was defined as conversion to arthroplasty or severely abnormal patient subjective IKDC score. RESULTS: Fifty-two patients (21M:31F) with a mean age of 58 ± 10 years were diagnosed with symptomatic MMPRTs clinically and confirmed by MRI and followed for a mean of 62 ± 30 months. Sixteen patients (31 %) underwent total knee arthroplasty at a mean of 30 ± 32 months after diagnosis with higher Kellgren-Lawrence grades associated with increased rates of arthroplasty (p = 0.01). Mean IKDC scores for the remaining patients were 61.2 ± 21 with significantly lower scores in females compared to males (75 ± 12 vs. 49 ± 20; p = 0.03). Mean Kellgren-Lawrence grades and rates of arthritis progressed over time on radiographs (1.5 ± 0.7 vs. 2.4 ± 1.0; p < 0.001 and 78 % vs. 51 %; p = 0.01). Overall, 87 % of patients failed non-operative treatment. CONCLUSIONS: Non-operative treatment of medial meniscus posterior horn root tears is associated with poor clinical outcome, worsening arthritis, and a relatively high rate of arthroplasty at 5-year follow-up. Female gender was associated with lower subjective scores and higher rate of arthroplasty. The current study provides a natural history benchmark for clinical outcomes that can be expected in patients with medial meniscus posterior horn root tears undergoing non-operative treatment and helps in counselling patients with these types of injuries. LEVEL OF EVIDENCE: IV.

Variable Reporting by Authors Presenting Arthroplasty Research at Multiple Annual Conferences.

BACKGROUND: Prior studies have demonstrated discrepancies in financial conflict of interest (COI) disclosure among authors presenting research at multiple spine and sports medicine conferences. The purpose of this study was to quantify the variability of self-reported financial disclosures of individual authors presenting at multiple arthroplasty conferences during the same year. METHODS: The author disclosure information published for the 2012 annual meetings of the American Academy of Orthopaedic Surgeons (AAOS), American Association of Hip and Knee Surgeons, the Hip Society, and the Knee Society were compiled. We tabulated the author disclosures, the number of companies/entities represented, and the types of disclosures reported. The disclosures made by authors presenting at more than one meeting were then compared for discrepancies. RESULTS: Of the 209 authors who presented at both the AAOS and American Association of Hip and Knee Surgeons meetings, 79 (37.79%) demonstrated discrepancies in their disclosures with 7 (8.8%) reporting no disclosures to the AAOS. Of the 84 authors who presented at both the AAOS and Hip Society meetings, 1 (1.19%) had discrepancies in their disclosures. Of the 52 authors who presented at both the AAOS and Knee Society meetings, 2 (3.84%) had discrepancies in their disclosures. CONCLUSION: There is variability in reported financial COIs by authors presenting at multiple arthroplasty conferences within the same year. Further work is warranted to improve transparency of COI disclosures among arthroplasty surgeons presenting research at national meetings.

Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.

PURPOSE: To redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD). METHODS: We present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1). RESULTS: The sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD. CONCLUSIONS: We have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD.

Evaluating online information regarding the direct anterior approach for total hip arthroplasty.

We evaluated the quality of information available on the Internet regarding the direct anterior approach (DAA). The top 50 Web sites from three major search engines (Google, Yahoo!, and Bing) were tabulated utilizing the search term direct anterior hip replacement. Of these, only 22% were authored by a hospital/university, while 60% were by a private physician/clinic. Most Web sites presented the DAA as "better" than other surgical approaches describing benefits, such as accelerated recovery though only 35% described risks of the approach. While only 39% of sites presented patient eligibility criteria, greater than 75% had the ability to make an appointment. Web sites regarding the DAA provide patients with a limited perspective and may be focused on attracting new patients, as opposed to accurately educating them.

District-Wise Heterogeneity in Blood Pressure Measurements, Prehypertension, Raised Blood Pressure, and Their Determinants Among Indians: National Family Health Survey-5.

Objective: The objective of the study was to determine the prevalence and determinants of ever-measured blood pressure, prehypertension, and raised blood pressure at national, state and district levels in India. Methods: We analysed data from the National Family Health Survey (NFHS-5), on 743,067 adults aged 18-54 years. The sample consisted of 87.6% females and 12.4% males. We estimated prevalence rates and determined adjusted odds ratios for various dependent variables related to blood pressure. Geographical variations were visualized on the map of India, and multivariate logistic regression was employed at state and district levels, with significance set at p < 0.05. Results: The prevalence of ever-measured blood pressure varied widely, from 30.3% to 98.5% across districts, with southern and northern regions showing higher rates. Prehypertension affected 33.7% of the population, with varying prevalence across districts. Raised blood pressure was there in 15.9%, with notably higher rates in southern region (16.8%). Determinants included age, gender, education, wealth, lifestyle, obesity, and blood glucose levels. Conclusion: These findings demonstrate the subnational variations in blood pressure, can guide evidence-based interventions at the state and district level, towards reducing the burden of raised blood pressure and enhancing overall population health.

Minimally Invasive Spine Surgery: Analyzing Internet-based Education Material.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: The purpose of this study is to evaluate the content of information available on the Internet regarding minimally invasive spine surgery (MISS). SUMMARY OF BACKGROUND DATA: Patients look to the Internet for quick and accessible information on orthopedic procedures to help guide their personal decision making process regarding the care they receive. However, the quality of internet-based orthopedic education material varies significantly with respect to accuracy and readability. MATERIALS AND METHODS: The top 50 results were generated from each of 3 search engines (Google, Yahoo!, and Bing) using the search term "minimally invasive spine surgery." Results were categorized by authorship type and evaluated for their description of key factors such as procedural benefits, risks, and techniques. Comparisons between search engines and between authorship types were done using the Freeman-Halton extension for the Fisher exact test. The content of websites certified by Health on the Net Foundation (HONcode) was compared with those not HONcode certified. RESULTS: Of the 150 websites and videos, only 26% were authored by a hospital or university, whereas 50% were by a private physician or clinic. Most resources presented some benefits of MISS (84%, 126/150), but only 17% presented risks of the procedure (26/150). Almost half of all resources described the technique of MISS, but only 27% had thorough descriptions that included visual representations while 26% failed to describe the procedure. Only 12 results were HONcode certified, and 10 (83%) of these were authored by a medical industry company. CONCLUSIONS: Internet-based resources on MISS provide inconsistent content and tend to emphasize benefits of MISS over risks.

Arthritis Progression on Serial MRIs Following Diagnosis of Medial Meniscal Posterior Horn Root Tear.

Medial meniscus posterior root tears (MMPRTs) are a significant source of pain and dysfunction. The purpose of this study was to evaluate changes in the medial compartment of the knee over time following the diagnosis of a MMPRT on MRI. A retrospective review of the institutional database was performed for patients with an initial MRI diagnosis of a MMPRT. Patients were included if they had a subsequent follow-up MRI on the same knee. Patients with surgical intervention, including debridement or repair, were excluded. MRIs were evaluated by two board-certified musculoskeletal radiologists. MMPRTs were defined using the LaPrade classification, and the medial compartment articular cartilage was graded using the modified Outerbridge classification. MRIs were reviewed for meniscus extrusion, subchondral bone edema, and insufficiency fractures. Patients were divided into two groups for the analysis to account for differences in MRI time intervals. Group 1 had a follow-up MRI within 12 months of initial imaging (subacute group) and Group 2 had a follow-up MRI greater than 12 months after initial imaging (chronic group). Forty-one knees and 82 MRIs were analyzed, including 20 knees/40 MRIs (13 females, 7 males) in the subacute group and 21 knees/42 MRIs (14 females, 7 males) in the chronic group. Subacute patients had a mean age of 59.5 ± 8.8 years and a mean interval of 4.8 ± 2.6 months between MRIs compared with 53.6 ± 11.0 years and 38.2 ± 20.8 months, respectively, for the chronic group. Meniscal extrusion, femoral modified Outerbridge grade, and tibial modified Outerbridge grade worsened between initial and final MRI in both groups (p < 0.05). In both groups, there were no significant differences between initial and final MRIs with regard to the LaPrade classification, insufficiency fracture, or subchondral cysts of the tibia. Progressive meniscus extrusion and medial compartment articular cartilage degeneration were seen in patients with MMPRTs within a year from diagnosis.

Virtual Screening of Chemical Compounds for Discovery of Complement C3 Ligands.

The complement system is our first line of defense against foreign pathogens, but when it is not properly regulated, complement is implicated in the pathology of several autoimmune and inflammatory disorders. Compstatin is a peptidic complement inhibitor that acts by blocking the cleavage of complement protein C3 to the proinflammatory fragment C3a and opsonin fragment C3b. In this study, we aim to identify druglike small-molecule complement inhibitors with physicochemical, geometric, and binding properties similar to those of compstatin. We employed two approaches using various high-throughput virtual screening methods, which incorporate molecular dynamics (MD) simulations, pharmacophore model design, energy calculations, and molecular docking and scoring. We have generated a library of 274 chemical compounds with computationally predicted binding affinities for the compstatin binding site of C3. We have tested subsets of these chemical compounds experimentally for complement inhibitory activity, using hemolytic assays, and for binding affinity, using microscale thermophoresis. As a result, although none of the compounds showed inhibitory activity, compound 29 was identified to exhibit weak competitive binding against a potent compstatin analogue, therefore validating our computational approaches. Additional docking and MD simulation studies suggest that compound 29 interacts with C3 residues, which have been shown to be important in binding of compstatin to the C3c fragment of C3. Compound 29 is amenable to physicochemical optimization to acquire inhibitory properties. Additionally, it is possible that some of the untested compounds will demonstrate binding and inhibition in future experimental studies.